The present embodiments relate to characterizing contrast agents. In particular, ultrasound distinguishes between different contrast agents, such as different types or different binding states.
Information at nonlinear frequencies, such as a cubic or nonlinear fundamental frequency, is detected by varying the transmit amplitude and phase associated with combined echo signals. Some techniques for detecting nonlinear fundamental information are disclosed in U.S. Pat. Nos. 6,494,841, 6,602,195, 6,632,177 and 6,682,482, the disclosures of which are incorporated herein by reference. The same or other nonlinear detection technique, such as phase or pulse inversion or pulse inversion Doppler, detects second harmonic nonlinear information. The nonlinear information, such as the nonlinear fundamental and second harmonic information, is generally specific to ultrasound contrast agents since contrast agents produce stronger nonlinear response and the transducer and tissue produce less nonlinear response. Some nonlinear detection techniques are more specific to contrast agents like those that detect nonlinear fundamental signals. The information provides improved tissue clutter rejection, allowing for imaging more specific to contrast agents. For example, small vessels within tissue may be more easily imaged or identified using nonlinear fundamental information.
U.S. Pat. No. 6,638,228, the disclosure of which is incorporated herein by reference, provides for contrast agent enhanced color-flow imaging. Power modulation or amplitude variation of the transmit pulses is used to obtain velocity information about moving contrast agents. A color Doppler estimator is used to detect the nonlinear signals from contrast agents with the purpose of suppressing signals from stationary or slowly moving objects.
Academic researchers and clinicians are working with contrast agents to detect, monitor response to therapy, and deliver drugs to diseased tissue such as atherosclerotic plaques in arteries. These studies utilize standard contrast agents as well as specially designed targeted contrast agents that bind to corresponding proteins on the endothelium or plaque. As one of many examples where contrast agents can be indicative of more than just where blood is flowing, contrast agents can attach to damaged endothelial cells within a vessel. Scanning electron microscopy and ultrasound contrast agent nonlinear fundamental information show contrast agents attached to a pig's carotid when the endothelium was damaged. Increased enhancement in contrast agent ultrasound detection is observed on the wall of the vessel. No contrast agents were observed attached to the control (non-injured) endothelium.